1har
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2.2 ANGSTROMS RESOLUTION STRUCTURE OF THE AMINO-TERMINAL HALF OF HIV-1 REVERSE TRANSCRIPTASE (FINGERS AND PALM SUBDOMAINS)
OverviewOverview
BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation, of single-stranded viral RNA into double-stranded DNA, which is integrated, into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence, of the amino-terminal subdomains of p66. Earlier crystallographic studies, indicate that the RT molecule is flexible, which may explain the, difficulty in obtaining high-resolution data for the intact protein. We, have therefore determined the structure of a fragment of RT (RT216), which, contains only the amino-terminal half of the RT molecule ('finger' and, 'palm' subdomains). RESULTS: The crystal structure of RT216 has been, refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The, structure is very similar to that of the corresponding part of the p66, subunit in the p66/p51 heterodimer, although there is a small difference, in the relative orientation of the two subdomains compared with the, structure of an RT-DNA-antibody fragment complex. There are a large number, of stabilizing contacts (mainly hydrogen bonds and hydrophobic, interactions) between the subdomains. The locations of conserved amino, acids and the position of some important drug-resistant mutations are, described. CONCLUSIONS: The RT216 structure provides detailed, three-dimensional information of one important part of HIV-1 RT (including, the critical active site residues). We propose a model to explain the, inhibitory effect of non-nucleoside inhibitors, which partially accounts, for their effect in terms of conformational changes of active site, residues.
About this StructureAbout this Structure
1HAR is a Single protein structure of sequence from Human immunodeficiency virus 1. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
ReferenceReference
2.2 A resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains)., Unge T, Knight S, Bhikhabhai R, Lovgren S, Dauter Z, Wilson K, Strandberg B, Structure. 1994 Oct 15;2(10):953-61. PMID:7532533
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